Reality CHEK: Understanding the biology and clinical potential of CHK112 Nov 2024 08:54
Paper from 2021 however the conclusions are worth a re-read!
Conclusion and future perspectives
Since its identification in 1993, CHK1 has been extensively studied and, although many questions remain, our understanding of its essential functions has rapidly improved. Significant strides towards elucidating the regulation, mechanism of action, and therapeutic potential of CHK1 have been made. The role of CHK1 in cell cycle regulation and the DDR presents a unique opportunity for therapeutic targeting. However, currently available CHK1 inhibitors have not yet fulfilled their promise either as monotherapy or radiosensitizers. Regardless, CHK1 targeting in cancer therapy remains a very promising prospect given the compelling results from preclinical evaluations. Much essential work remains to fully understand CHK1 regulation, substrate specificity, and identify novel CHK1 substrates. The ability of CHK1 inhibitors to sensitize to a wide range of DNA damaging agents is not in doubt; the more compelling issue is the identification of robust predictive and pharmacodynamic biomarkers to enhance clinical realization of CHK1 inhibitors. New generations of pharmacologic CHK1 inhibitors must focus on improving bioavailability, reducing toxicity, and increasing specificity. Additionally, novel approaches are needed to target CHK1 by non-conventional means. For example, regulators of CHK1 kinase activation and substrate targeting present interesting new avenues. The success of future CHK1 -targeted therapies depends on vigorous research to identify novel regulators of CHK1 as well as mechanistic investigation of CHK1 substrate targeting.
https://www.sciencedirect.com/science/article/pii/S0304383520304857
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